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Enzyme Responsible For Congenital Blindness

Researchers from UCLA had found out that a deficient gene that is also responsible for the presence of an enzyme in the vision cycle that causes congenital blindness in children. The researchers’ study regarding the congenital blinding disease // called Leber congenital amaurosis is published in the August issue of the journal Cell.

Researchers suggest that replacement of RPE65, which is lacking in these patients, by gene therapy should correct the blindness in these children, as was observed in mice and dogs with RPE65 mutations, said the researchers. This is a major breakthrough in understanding the visual cycle. It has ramifications for several inherited blinding diseases caused by mutations in visual cycle genes.

The newly identified isomerase enzyme plays a crucial role in the regeneration of rhodopsin visual pigment in the retina after light exposure. Rhodopsin contains a light-absorbing molecule called 11 cis retinaldehyde, related to vitamin A, which is converted upon light absorption to all trans retinaldehyde in a process called photo bleaching. This conversion is the first step in visual perception.

Photo bleaching leaves the rhodopsin insensitive to light until the all trans retinaldehyde is converted, or "isomerized," back into 11 cis retinaldehyde, which completes the visual cycle. Scientists have for two decades been attempting to identify the retinoid isomerase enzyme that catalyzes this regeneration of 11 cis retinaldehyde. Scientists have also been stumped by the function of the Rpe65 protein

The researchers had performed an expression screen in cultured human cells, looking for a gene that caused these cells to convert vitamin A into 11 cis retinol.

The researchers are now studying the effects on retinoid isomerase activity of specific disease causing mutations in the RPE65 gene, which should provide more data on the cause of Leber congenital amaurosis and on how the Rpe65 protein works. The
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